Drug interactions
Clomipramine + Methadone
Severity: Major
Clomipramine and Methadone: major interaction.
Last updated Sources: US FDA label
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Clomipramine can prolong the QT interval and add to methadone's arrhythmic risk, and both drugs cause sedation. Clomipramine also has serotonergic activity and may inhibit CYP2D6, which can increase methadone exposure.
What this interaction means in plain words
Clomipramine and Methadone can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Clomipramine belongs to Central Nervous System; Methadone belongs to Musculoskeletal.
Why it happens
Additive QT prolongation and CNS depression, with possible CYP2D6 inhibition and additive serotonergic effects.
What to do
Obtain a baseline ECG and monitor the QTc, and correct potassium and magnesium. Monitor for sedation and serotonin toxicity, and consider an alternative antidepressant.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
Other interactions of Methadone
- Alvimopan + Methadone Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Methadone Contraindicated
- Droperidol + Methadone Contraindicated
- Ibutilide + Methadone Contraindicated
- Isocarboxazid + Methadone Contraindicated
- Lefamulin + Methadone Contraindicated
Other interactions of Clomipramine
- Arsenic trioxide + Clomipramine Contraindicated
- Clomipramine + Dofetilide Contraindicated
- Clomipramine + Droperidol Contraindicated
- Clomipramine + Isocarboxazid Contraindicated
- Clomipramine + Methylene blue Contraindicated
- Clomipramine + Pentamidine Contraindicated
Frequently asked questions
Can I take Clomipramine with Methadone?
MediHelp rates the interaction as major. Clomipramine and Methadone can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Clomipramine can prolong the QT interval and add to methadone's arrhythmic risk, and both drugs cause sedation. Clomipramine also has serotonergic activity and may inhibit CYP2D6, which can increase methadone exposure.
How serious is the interaction between Clomipramine and Methadone?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Obtain a baseline ECG and monitor the QTc, and correct potassium and magnesium. Monitor for sedation and serotonin toxicity, and consider an alternative antidepressant.
What other medicines interact with Methadone?
MediHelp also lists interactions of Methadone with, for example, Alvimopan, Calcium / magnesium / potassium / sodium oxybates, Droperidol. The full list is on the Methadone page.
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